INPHARMA

Development of an innovative anti-inflammatory drug

with a novel mechanism of action – inhibitor of inducible NO-

synthase

Problem. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in medicine. Every year over 300 million people use them. All NSAIDs have one target – cyclooxygenase (COX), an enzyme responsible for prostaglandin synthesis. Due to this NSAIDs have adverse ulcerogenic effect on gastointestinal mucosa, possibly causing dangerous bleedings. NSAIDs use causes 103 000 hospitalizations and 16500 deaths a year in USA alone.

Solution. Development of an anti-inflammatory drug with a new mechanism of action, not related to inhibition of COX, will solve this problem. The solution is based on a new molecule, created under leadership of professor V. Granik. The new molecule is a derivative of aminoguanidine – the best selective inhibitor of inducible NO-synthase, bonded with a structural component – a “carrier”, which ensures high bioavailability of the drug in oral use, high potency and better safety profile.

Technology is based on selective inhibition of inducible NO-synthase (iNOS). This isoform of the enzyme catalyzes excessive production of nitric oxide, which is a main mechanism of pathological inflammation. Experiments (on peritonitis models) have proven the new compound’s potent anti-inflammatory activity. The compound’s safety is proven – its LD50 > 5000 mg/kg (mice, per os) which is much better than LD50 values of the known NSAIDs (diclofenac, indomethacin, etc.).

Problem & Solution

World market. In 2010 world sales of NSAIDS (Anti-Reumatics, Non-Steroidal, according to IMS Health data) amounted to $10.15 billion. Sales leader - Celebrex (Pfizer) – $2.49 billion.

Competitors:

1) Classic NSAIDs (non-selective COX inhibitors) –have gastrointestinal adverse effects.

2) Selective COX-2 inhibitors: coxibs (Celebrex, etc.), nimesulide - cause complications of cardiovascular system, increased liver and kidney toxicity.

Advantages:

The new drug does not inhibit COX activity, so it does not cause adverse ulcerogenic effects that lead to hospitalizations and deaths of many patients using NSAIDs.

Potential customers – “Big Pharma” companies, interested in market launch of a novel NSAID – iNOS inhibitor exhibiting high effectiveness, selectivity, high bioavailability in oral use and good toxicity and adverse effects profile.

Business model provides for licensing the development after finishing Phase I and II clinical trials in Russia (2016-2017) with transferring rights to a strategic investor(s) (Russian pharmaceutical company, “Big Pharma” company) for certain markets. Planned volume of deals (license agreements), including up-front and milestone payments – at least $100 million.

Market & Business model

TeamLeader:

Khazanov Veniamin, professor, PhD, an expert in drug development and commercialization. Since 1991 he has been doing high technology business, has 20 years of experience in organizing and managing projects of drug development for medical purposes. Creator and head of “iPhar” group of companies - one of the leading Russian centers of drug development.

Science team, key persons:

Belska Nataly, PhD - pharmacologist, immunologist. Work experience: Scientific Institute of Pharmacology of Siberian Branch of Russian Academy of Medical Sciences – head of Department of Experimental Biological Models, ZAO “INPHARMA” – director of preclinical trials. Responsibility: organization and control of preclinical trials of the drug.

Joseph Schwarz, PhD - world-class expert in the fields of pharmaceutical technology, drug formulation and manufacturing technology (Canada). Formerly one of the heads of formulation department of TEVA (Israel). Advisor on pharmaceutical development of the substance and dosage forms of the anti-inflammatory drug.

Project needs

R&D platform

INPHARMA has the necessary resources (laboratories, equipment and staff) for developing laboratory synthesis technology of the substance for the new drug, production of test samples for preclinical trials, studying its pharmacological activity.

IPHAR company is the main partner (R&D platform) for preclinical trials and dosage form development of the new drug as well as for IP protection issues and project commercialization. IPHAR has the necessary material resources, qualified staff and established network of partnerships with higher education institutes, scientific institutes and clinical centers of Russia, foreign organizations and specialists from UK, Sweden, Italy, Canada, USA, Israel and other countries.

Financial needs

Co-investments (about 20 million rub.) and grant funding (20 million rub.) - for performing preclinical trials of the new drug.